| Summary: | <i>Pseudomonas aeruginosa</i> is one of the most dominant pathogens in cystic fibrosis (CF) airway disease and contributes to significant inflammation, airway damage, and poorer disease outcomes. The CF airway is now known to be host to a complex community of microorganisms, and polymicrobial interactions have been shown to play an important role in shaping <i>P. aeruginosa</i> pathogenicity and resistance. <i>P. aeruginosa</i> can cause chronic infections that once established are almost impossible to eradicate with antibiotics. CF patients that develop chronic <i>P. aeruginosa</i> infection have poorer lung function, higher morbidity, and a reduced life expectancy. <i>P. aeruginosa</i> adapts to the CF airway and quickly develops resistance to several antibiotics. A perplexing phenomenon is the disparity between in vitro antimicrobial sensitivity testing and clinical response. Considering the CF airway is host to a diverse community of microorganisms or ‘microbiome’ and that these microorganisms are known to interact, the antimicrobial resistance and progression of <i>P. aeruginosa</i> infection is likely influenced by these microbial relationships. This review combines the literature to date on interactions between <i>P. aeruginosa</i> and other airway microorganisms and the influence of these interactions on <i>P. aeruginosa</i> tolerance to antimicrobials.
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